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1.
J Neurol Neurosurg Psychiatry ; 87(8): 885-9, 2016 Aug.
Article in English | MEDLINE | ID: mdl-26917698

ABSTRACT

BACKGROUND: Natalizumab (NTZ), a monoclonal antibody to human α4ß1/ß7 integrin, is an effective therapy for multiple sclerosis (MS), albeit associated with progressive multifocal leukoencephalopathy (PML). Clinicians have been extending the dose of infusions with a hypothesis of reducing PML risk. The aim of the study is to evaluate the clinical consequences of reducing NTZ frequency of infusion up to 8 weeks 5 days. METHODS: A retrospective chart review in 9 MS centres was performed in order to identify patients treated with extended interval dosing (EID) regimens of NTZ. Patients were stratified into 3 groups based on EID NTZ treatment schedule in individual centres: early extended dosing (EED; n=249) every 4 weeks 3 days to 6 weeks 6 days; late extended dosing (LED; n=274) every 7 weeks to 8 weeks 5 days; variable extended dosing (n=382) alternating between EED and LED. These groups were compared with patients on standard interval dosing (SID; n=1093) every 4 weeks. RESULTS: 17% of patients on SID had new T2 lesions compared with 14% in EID (p=0.02); 7% of patients had enhancing T1 lesions in SID compared with 9% in EID (p=0.08); annualised relapse rate was 0.14 in the SID group, and 0.09 in the EID group. No evidence of clinical or radiographic disease activity was observed in 62% of SID and 61% of EID patients (p=0.83). No cases of PML were observed in EID group compared with 4 cases in SID cohort. CONCLUSIONS: Dosing intervals up to 8 weeks 5 days did not diminish effectiveness of NTZ therapy. Further monitoring is ongoing to evaluate if the risk of PML is reduced in patients on EID.


Subject(s)
Leukoencephalopathy, Progressive Multifocal/chemically induced , Leukoencephalopathy, Progressive Multifocal/prevention & control , Multiple Sclerosis/drug therapy , Natalizumab/administration & dosage , Natalizumab/therapeutic use , Adult , Drug Administration Schedule , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Natalizumab/adverse effects , Neuroimaging , Recurrence , Retrospective Studies
2.
Am J Transplant ; 15(8): 2256-60, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25872800

ABSTRACT

Lung transplantation (LTx) may be denied for children on extracorporeal membrane oxygenation (ECMO) due to high risk of cerebral hemorrhage. Rarely has successful LTx been reported in children over 10 years of age receiving awake or ambulatory veno-venous ECMO. LTx following support with ambulatory veno-arterial ECMO (VA ECMO) in children has never been reported to our knowledge. We present the case of a 4-year-old, 12-kg child with heritable pulmonary artery hypertension and refractory right ventricular failure. She was successfully bridged to heart-lung transplantation (HLTx) using ambulatory VA ECMO. Initial resuscitation with standard VA ECMO was converted to an ambulatory circuit using Berlin heart cannulae. She was extubated and ambulating around her bed while on VA ECMO for 40 days. She received an HLTx from an oversized marginal lung donor. Despite a cardiac arrest and Grade 3 primary graft dysfunction, she made a full recovery without neurological deficits. She achieved 104% force expiratory volume in 1 s 33 months post-HLTx. Ambulatory VA ECMO may be a useful strategy to bridge very young children to LTx or HLTx. Patient tailored ECMO cannulation, minimization of hemorrhage, and thrombosis risks while on ECMO contributed to a successful HLTx in our patient.


Subject(s)
Extracorporeal Membrane Oxygenation , Heart Transplantation , Lung Transplantation , Child, Preschool , Female , Humans
3.
Can J Cardiol ; 29(12): 1535-1552, dec. 2013.
Article in English | BIGG - GRADE guidelines | ID: biblio-965277

ABSTRACT

Pediatric heart failure (HF) is an important cause of morbidity and mortality in childhood. This article presents guidelines for the recognition, diagnosis, and early medical management of HF in infancy, childhood, and adolescence. The guidelines are intended to assist practitioners in office-based or emergency room practice, who encounter children with undiagnosed heart disease and symptoms of possible HF, rather than those who have already received surgical palliation. The guidelines have been developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, and are accompanied by practical Recommendations for their application in the clinical setting, supplemented by online material. This work does not include Recommendations for advanced management involving ventricular assist devices, or other device therapies.


Subject(s)
Humans , Infant , Child, Preschool , Child , Heart Defects, Congenital , Heart Failure , Vasodilator Agents , Algorithms , Vasopressins , Angiotensin-Converting Enzyme Inhibitors , Echocardiography , Biomarkers/blood , Cardiotonic Agents , Catecholamines/therapeutic use , Electrocardiography, Ambulatory , Death, Sudden, Cardiac/etiology , Death, Sudden, Cardiac/prevention & control , Angiotensin II Type 1 Receptor Blockers/therapeutic use , Diuretics , Heart Defects, Congenital/diagnosis , Heart Defects, Congenital/therapy , Myocarditis , Myocardium/pathology
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